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Competing Interests: Conflict of interest statement All authors are current/past members of the GOLD Scientific Committee but declare that none has a conflict of interest in relation to this manuscript.

Background: Many diseases leave behind specific metabolites which can be detected from breath and urine as volatile organic compounds (VOC). Our group previously described VOC-based methods for the detection of bladder cancer and urinary tract infections. This study investigated whether prostate cancer can be diagnosed from VOCs in urine headspace., Methods: For this pilot study, mid-stream urine samples were collected from 56 patients with histologically confirmed prostate cancer. A control group was formed with 53 healthy male volunteers matched for age who had recently undergone a negative screening by prostate-specific antigen (PSA) and digital rectal exam. Headspace measurements were performed with the electronic nose Cyranose 320 TM . Statistical comparison was performed using principal component analysis, calculating Mahalanobis distance, and linear discriminant analysis. Further measurements were carried out with ion mobility spectrometry (IMS) to compare detection accuracy and to identify potential individual analytes. Bonferroni correction was applied for multiple testing., Results: The electronic nose yielded a sensitivity of 77% and specificity of 62%. Mahalanobis distance was 0.964, which is indicative of limited group separation. IMS identified a total of 38 individual analytical peaks, two of which showed significant differences between groups (p < 0.05). To discriminate between tumor and controls, a decision tree with nine steps was generated. This model led to a sensitivity of 98% and specificity of 100%., Conclusions: VOC-based detection of prostate cancer seems feasible in principle. While the first results with an electronic nose show some limitations, the approach can compete with other urine-based marker systems. However, it seems less reliable than PSA testing. IMS is more accurate than the electronic nose with promising sensitivity and specificity, which warrants further research. The individual relevant metabolites identified by IMS should further be characterized using gas chromatography/mass spectrometry to facilitate potential targeted rapid testing., (© 2024 The Authors. The Prostate published by Wiley Periodicals LLC.)

E-cigarettes are primarily used by teenagers and young adults. Flavors in e-cigarettes increase their attractiveness and encourage young people and adults to start using them. This exposes young people in particular to the risk of nicotine addiction and various toxic substances from the aerosol of e-cigarettes. There are indications that various flavors in e-cigarettes are harmful to health, although toxicological studies are still lacking for the majority of flavors. There is a need for independent scientific investigations in this area. The scientific societies involved are calling for a ban on flavors in e-cigarettes, a ban on disposable e-cigarettes, effective regulation of the sale of e-cigarettes and effective control and implementation of the provisions for the protection of minors., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Introduction: SARS-CoV-2 is usually diagnosed from naso-/oropharyngeal swabs which are uncomfortable and prone to false results. This study investigated a novel diagnostic approach to Covid-19 measuring volatile organic compounds (VOC) from patients' urine., Methods: Between June 2020 and February 2021, 84 patients with positive RT-PCR for SARS-CoV-2 were recruited as well as 54 symptomatic individuals with negative RT-PCR. Midstream urine samples were obtained for VOC analysis using ion mobility spectrometry (IMS) which detects individual molecular components of a gas sample based on their size, configuration, and charge after ionization., Results: Peak analysis of the 84 Covid and 54 control samples showed good group separation. In total, 37 individual specific peaks were identified, 5 of which (P134, 198, 135, 75, 136) accounted for significant differences between groups, resulting in sensitivities of 89-94% and specificities of 82-94%. A decision tree was generated from the relevant peaks, leading to a combined sensitivity and specificity of 98% each., Discussion: VOC-based diagnosis can establish a reliable separation between urine samples of Covid-19 patients and negative controls. Molecular peaks which apparently are disease-specific were identified. IMS is an additional non-invasive and cheap device for the diagnosis of this ongoing endemic infection. Further studies are needed to validate sensitivity and specificity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: The impact of occupational exposures on lung function impairments and quality of life (QoL) in patients with chronic obstructive pulmonary disease (COPD) was analysed and compared with that of smoking., Methods: Data from 1283 men and 759 women (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4 or former grade 0, without alpha-1-antitrypsin deficiency) of the COPD and Systemic Consequences Comorbidities Network cohort were analysed. Cumulative exposure to gases/fumes, biological dust, mineral dust or the combination vapours/gases/dusts/fumes was assessed using the ALOHA job exposure matrix. The effect of both occupational and smoking exposure on lung function and disease-specific QoL (St George's Respiratory Questionnaire) was analysed using linear regression analysis adjusting for age, body mass index, diabetes, hypertension and coronary artery disease, stratified by sex., Results: In men, exposure to gases/fumes showed the strongest effects among occupational exposures, being significantly associated with all lung function parameters and QoL; the effects were partially stronger than of smoking. Smoking had a larger effect than occupational exposure on lung diffusing capacity (transfer factor for carbon monoxide) but not on air trapping (residual volume/total lung capacity). In women, occupational exposures were not significantly associated with QoL or lung function, while the relationships between lung function parameters and smoking were comparable to men., Conclusions: In patients with COPD, cumulative occupational exposure, particularly to gases/fumes, showed effects on airway obstruction, air trapping, gas uptake capacity and disease-related QoL, some of which were larger than those of smoking. These findings suggest that lung air trapping and QoL should be considered as outcomes of occupational exposure to gases and fumes in patients with COPD., Trial Registration Number: NCT01245933., Competing Interests: Competing interests: DN received honoraria for lectures from Bristol Myers Squibb, Berlin Chemie, Boehringer Ingelheim, Chiesi, GlaxoSmithKline (GSK), Mundipharma, Novartis, Hexal and Lilly. Moreover, he received payments for expert testimony from courts and social accident insurances and institutional travel support from LMU Munich and reports personal stocks (mixed). SK received grants (82DZL083B2) from the German Center for Lung Research (DZL). Within the past 36 months, CV received grants or contracts from the German Ministry of Education and Science (BMBF) and from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GSK, Grifols and Novartis. Moreover, he received consulting fees from Aerogen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GSK, Insmed, Menarini, Novartis and Nuvaira, and payments for lectures, presentations, speaker bureaus, manuscript writing or educational events from Aerogen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GSK, Insmed, Menarini, Novartis, Roche and Sanofi. UO is the chair of the Committee for Maternity Protection (Ausschuss für Mutterschutz), Bundesministerium für Familie, Senioren, Frauen und Jugend (BMFSFJ). She received payments from GSK for a lecture on vaccination in health settings, from Sozial- und Arbeitsmedizinische Akademie Baden-Württemberg (SAMA) for a lecture on maternity protection and from Akademie für Gesundheit und Lebensmittelsicherheit im Bayerischen Landesamt für Gesundheit und Lebensmittelsicherheit for a lecture on maternity protection. She received support for attending meetings/travel from BMJSFJ and from the LMU University Hospital, LMU Munich. HK is the editor-in-chief of Occupational and Environmental Medicine., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The prevalence and clinical profile of asthma with airflow obstruction (AO) remain uncertain. We aimed to phenotype AO in population- and clinic-based cohorts., Methods: This cross-sectional multicohort study included adults ≥50 years from nine CADSET cohorts with spirometry data (N=69 789). AO was defined as ever diagnosed asthma with pre-BD or post-BD FEV 1 /FVC <0.7 in population-based and clinic-based cohorts, respectively. Clinical characteristics and comorbidities of AO were compared with asthma without airflow obstruction (asthma-only) and chronic obstructive pulmonary disease (COPD) without asthma history (COPD-only). ORs for comorbidities adjusted for age, sex, smoking status and body mass index (BMI) were meta-analysed using a random effects model., Results: The prevalence of AO was 2.1% (95% CI 2.0% to 2.2%) in population-based, 21.1% (95% CI 18.6% to 23.8%) in asthma-based and 16.9% (95% CI 15.8% to 17.9%) in COPD-based cohorts. AO patients had more often clinically relevant dyspnoea (modified Medical Research Council score ≥2) than asthma-only (+14.4 and +14.7 percentage points) and COPD-only (+24.0 and +5.0 percentage points) in population-based and clinic-based cohorts, respectively. AO patients had more often elevated blood eosinophil counts (>300 cells/µL), although only significant in population-based cohorts. Compared with asthma-only, AO patients were more often men, current smokers, with a lower BMI, had less often obesity and had more often chronic bronchitis. Compared with COPD-only, AO patients were younger, less often current smokers and had less pack-years. In the general population, AO patients had a higher risk of coronary artery disease than asthma-only and COPD-only (OR=2.09 (95% CI 1.26 to 3.47) and OR=1.89 (95% CI 1.10 to 3.24), respectively) and of depression (OR=1.41 (95% CI 1.19 to 1.67)), osteoporosis (OR=2.30 (95% CI 1.43 to 3.72)) and gastro-oesophageal reflux disease (OR=1.68 (95% CI 1.06 to 2.68)) than COPD-only, independent of age, sex, smoking status and BMI., Conclusions: AO is a relatively prevalent respiratory phenotype associated with more dyspnoea and a higher risk of coronary artery disease and elevated blood eosinophil counts in the general population compared with both asthma-only and COPD-only., Competing Interests: Competing interests: LL reports consulting fees from AstraZeneca and speaking/lecture fees from Chiesi and IPSA (non-profit) outside the submitted work. CHV reports presentations at symposia and/or served on scientific advisory boards sponsored by Aerogen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GlaxoSmithKline, Grifols, Insmed, Menarini, Novartis, Nuvaira, MedUpdate, Sanofi and Roche outside the submitted work. AA reports grants from GSK, AstraZeneca and Menarini and speaking/lecture fees from GSK, AstraZeneca, Chiesi, Menarini, CIPLA, Zambon, and Sanofi Regeneron outside the submitted work, and is chair of the GOLD board of directors. JAW reports grants from AstraZeneca, Boehringer-Ingelheim, Chiesi, GSK, Novartis, Genentech, and 37Clinical, advisory board fees from AstraZeneca, Epiendo, GSK, Gilead, Novartis, Pieris and Pulmatrix, speaker fees from AstraZeneca, GSK, Boehringer, Recipharm and Novartis, and DSMB chair for Virtus outside the submitted work, and is Editor in Chief of AJRCCM. GGB reports fees for advisory boards and/or lectures from AstraZeneca, Boehringer-Ingelheim, Chiesi, GSK, Merck Sharp & Dohme, Novartis, and Sanofi Regeneron outside the submitted work. HB reports personal fees from AstraZeneca, Boehringer Ingelheim, and GlaxoSmithKline for presentations at scientific meetings outside the submitted work. AL reports speaking/lecture fees from Boehringer-Ingelheim and Novartis, and participation on a advisory board for AstraZeneca, GSK, Novartis, and Boehringer-Ingelheim outside the submitted work. KFC reports advisory board fees from GSK, AstraZeneca, Roche, Novartis, Merck, Nocion, Shionogi and Rickett-Beckinson and has been renumerated for speaking engagements for GSK, AstraZeneca and Merck outside the submitted work. IMA reports investigator-led awards from GSK and Sanofi in addition to travel awards, speakers' fees and advisory board fees from AZ, Chiesi, GSK, Eurodrug, Kineset, Sanofi and Sunovion outside the submitted work. None declared (XB, AE, JG-A, RF, HM, TS, PA, NO, NZK, GCD, ER, JMV and MvdB)., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Exposure to air pollution is a major contributor to the pathogenesis of COPD worldwide. Indeed, most recent estimates suggest that 50% of the total attributable risk of COPD may be related to air pollution. In response, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Scientific Committee performed a comprehensive review on this topic, qualitatively synthesised the evidence to date and proffered recommendations to mitigate the risk. The review found that both gaseous and particulate components of air pollution are likely contributors to COPD. There are no absolutely safe levels of ambient air pollution and the relationship between air pollution levels and respiratory events is supra-linear. Wildfires and extreme weather events such as heat waves, which are becoming more common owing to climate change, are major threats to COPD patients and acutely increase their risk of morbidity and mortality. Exposure to air pollution also impairs lung growth in children and as such may lead to developmental COPD. GOLD recommends strong public health policies around the world to reduce ambient air pollution and for implementation of public warning systems and advisories, including where possible the use of personalised apps, to alert patients when ambient air pollution levels exceed acceptable minimal thresholds. When household particulate content exceeds acceptable thresholds, patients should consider using air cleaners and filters where feasible. Air pollution is a major health threat to patients living with COPD and actions are urgently required to reduce the morbidity and mortality related to poor air quality around the world., Competing Interests: Conflict of interest: There was no external funding for the submitted work. D.D. Sin reports receipt of honorarium from AstraZeneca, GlaxoSmithKline and Boehringer Ingelheim for giving talks on COPD, and participation on an advisory board for an NHLBI-sponsored trial. A. Agusti reports grants from AstraZeneca, GlaxoSmithKline, Menarini, Sanofi and Chiesi, and receipt of consulting fees and honoraria for presentations from AstraZeneca, GlaxoSmithKline, Chiesi, Menarini, Sanofi and Zambon. F.J. Martinez reports grants from AstraZeneca, Chiesi, GlaxoSmithKline and Sanofi/Regeneron, receipt of consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Bering, GlaxoSmithKline, Novartis, Polarean, Pulmonx, Sanofi, Regeneron, Sunovion, Teva, Theravance and UptoDate, honoraria for presentations from AstraZeneca and GlaxoSmithKline, and advisory board participation with MedTronic and GlaxoSmithKline. A. Anzueto reports receipt of consulting fees from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim and Viatix/Theravance. B.R. Celli reports receipt of consulting fees from GlaxoSmithKline, AstraZeneca, Axios, Menarini and Sanofi, honoraria for presentations from GlaxoSmithKline, AstraZeneca, Menarini, Chiesi and Regeneron, travel support from GlaxoSmithKline and Sanofi, and advisory board participation for AstraZeneca Therapeutics, Sanofi Aventis and Vertx. D. Halpin reports receipt of honoraria for presentations from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Pfizer, Sanofi, Berlin-Chemie and Menarini, travel support from Menarini, and advisory board participation with Chiesi, GlaxoSmithKline and Inogen. M.K. Han reports grants from the NIH, Sanofi, Novartis, Nuvaira, Sunovion, Gala Therapeutics, COPD Foundation, AstraZeneca, American Lung Association, Boehringer Ingelheim and Biodesix, consulting fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pulmonox, Teva, Verona, Merck, Mylan, Sanofi, DevPro, Aerogen, Polarian, United Therapeutics, Regeneron, Altesa Biopharma and Amgen, honoraria for presentations from Cipla, Chiesi, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Medscape, Integrity and NACE, royalties from UptoDate, Norton Publishing and Penguin Random House, advisory board membership for Novartis and Medtronic, leadership roles with the COPD Foundation (board), COPD Foundation (scientific advisory committee), ALA (advisory committee), American Thoracic Society (journal editor), ALA (volunteer spokesperson), GOLD (scientific committee) and Emerson School Board, Ann Arbor, MI, stock or stock options from Meissa Vaccines and Altesa BioPharma, writing support from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca and Novartis, and other personal fees from Medscape and Integrity. A. Papi reports grants from Chiesi, AstraZeneca, GlaxoSmithKline, Sanofi and Agenzia Italiana del Farmaco (AIFA), receipt of consulting fees from Chiesi, AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Avillion and Elpen Pharmaceuticals, honoraria for presentations from Chiesi, AstraZeneca, GlaxoSmithKline, Menarini, Novartis, Zambon, Mundipharma, Sanofi, Edmond Pharma, Iqvia, Avillion and Elpen Pharmaceuticals, and advisory board participation for Chiesi, AstraZeneca, GlaxoSmithKline, MSD, Novartis, Sanofi, Iqvia, Avillion and Elpen Pharmaceuticals. I. Pavord reports grants from Chiesi, receipt of consulting fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Regeneron, Sanofi, Teva, Circassia, Dey Pharma, Genentech, Knopp Biosciences, Merck, MSD, Napp Pharmaceuticals, RespiVert and Schering-Plough, and honoraria for presentations from Aerocrine BB, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Regeneron, Sanofi and Teva. N. Roche reports grants from Boehringer Ingelheim, Novartis, GlaxoSmithKline and Pfizer, receipt of consulting fees from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Sanofi, Chiesi, Pfizer, Novartis, Teva and Bayer, and honoraria for presentations from Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Sanofi, Chiesi, Pfizer, Novartis, Teva, Zambon and MSD. D. Singh reports receipt of consulting fees from Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Bering, Epiendo, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, Pulmatrix, Sanofi, Synairgen, Teva, Theravance and Verona, outside of the submitted work. R. Stockley reports receipt of consulting fees from Vertex, CSL Bering and Mereo Biopharma, and data safety monitoring board participation with Syneos. J. Wedzicha reports grants from AstraZeneca, Boehringer, Chiesi, GlaxoSmithKline, Novartis, Genentech and 37Clinical, receipt of consulting fees from AstraZeneca, Epiendo, GlaxoSmithKline, Gilead, Novartis, Pieris and Pulmatrix, honoraria for presentations from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Recipharm and Novartis, and data safety monitoring board participation with Virtus. C. Vogelmeier reports grants from AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GlaxoSmithKline, Grifols and, Novartis, and personal fees from AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GlaxoSmithKline, Grifols, Menarini, Novartis, Nuvaira, MedUpdate, Aerogen, Roche, Sanofi and Insmed, outside of the submitted work. J. Bourbeau reports grants from the Canadian Institute of Heath Research (CIHR), Réseau en santé respiratoire du FRQS, McGill University, McGill University Health Centre Foundation, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Grifols, Novartis, Sanofi and Trudell Canada Ltd, and receipt of honoraria from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Trudell and COVIS Pharma for presentations, outside of the submitted work. The remaining authors disclose no potential conflicts of interest., (Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.)

COSYCONET 1 is the only German COPD cohort which is large enough to be internationally comparable. The recruitment, which started in 2010 and ended in December 2013, comprised 2741 patients with the diagnosis of COPD who were subsequently investigated in regular follow-up visits. All visits included a comprehensive functional and clinical characterisation. On the basis of this detailed data set, it was possible to address a large number of clinical questions. These questions ranged from the prescription of medication, the detailed analysis of comorbidities, in particular cardiovascular disease, and biomarker assessment to radiological and health-economic aspects. Currently, more than 60 publications of COSYCONET data are internationally available. The present overview provides a description of all the results that were obtained, focussing on the relationship between different clinical and functional aspects as well as their potential practical consequences. In addition, information on the follow-up study COSYCONET 2 is given., Competing Interests: Kathrin Kahnert berichtet persönliche Einnahmen über Vortragstätigkeiten der Fa. Astra Zeneca und GSK, welche nicht in Zusammenhang mit der COSYCONET-Studie stehen. Carolina Fischer, Jürgen Behr, Rudolf Jörres, Felix, Herth, Sandra Söhler, Henrik Watz, Inge Kokot, Peter Alter berichten keine Interessenskonflikte. Klaus Rabe berichtet persönliche Einnahmen für Vortragstätigkeiten von Astra Zencea, Boehringer Ingelheim, Chiesie Pharmaceuticals, Novartis, Sanofi & Regeneron, GlaxoSmithKline, Berlin Chemie, Roche Pharma sowie die Teilnahme an Advisory Boards bei Astra Zeneca, Boerhinger Ingelheim und Sanofi & Regeneron, welche nicht in Zusammenhang mit der COSYCONET-Studie stehen. Claus Vogelmeier berichtet über Verträge zwischen dem BMBF, Astra Zeneca, Boehringer Ingelheim, Chiesie, CSL Behring, GlaxoSmithKline, Grifols, Novartis und der Philipps-Universität Marburg, zudem persönliche Einnahmen über Vortragstätigkeiten/Beratungen bei den Firmen Aerogen, Astra Zeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GlaxoSmithKline, Insmed Menarini, Novartis, Nuvaira, Insmed Menarini, außerhalb der vorliegenden Arbeit. Franziska Trudzinski berichtet persönliche Einnahmen über Vortragstätigkeiten der Fa. Boehringer Ingelheim, Chiesie, GlaxoSmithKline, Grifols, Novartis, CSL Behring, welche nicht in Zusammenhang mit der COSYCONET-Studie stehen. Tobias Welte berichtet über Verträge zwischen dem BMBF, GSK, Novartis, Astra Zeneca, Boehringer Ingelheim und der Medizinischen Hochschule Hannover, zudem persönliche Einnahmen über Vortragstätigkeiten/Beratungen für Astra Zeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesie, GSK, Novartis außerhalb der vorliegenden Arbeit. Hans-Ulrich Kauczor berichtet Unterstützung der Fa. Bayer an die Universität Heidelberg (Verbrauchsmaterial), Verträge zwischen den Fa. Philips, Siemens und Boehringer Ingelheim zu der Universität Heidelberg, ferner persönliche Einnahme über Vortrags- und Beratertätigkeiten bei Siemens, Philips, Boehringer Ingelheim, MSD, Sanofi außerhalb der hier eingereichten Arbeit. Robert Bals berichtet persönliche Einnahmen über Vortrags- und Beratertätigkeiten von AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Grifols, Novartis, CSL Behring sowie Fördermittel für das Institut des BMBF, des Competence Network Asthma and COPD (ASCONET), Sander Stiftung, Schwiete Stiftung, Krebshilfe, Mukoviszidose e.V. außerhalb der eingereichten Arbeit., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide; many recent advances have been made in many aspects of the disease. The aim of this article is to illustrate and discuss some of these advances in the management of different types of patients. Large-scale trials have confirmed that long-acting bronchodilator therapy, particularly using the combination of LABA/LAMA, remains the mainstay of COPD treatment, with special attention being paid to careful selection of inhaler devices. The initial choice of pharmacological therapy is based on the GOLD ABCD grouping of patients. It is very important to stress that there is a need to implement a management cycle because COPD is a chronic disease with varying clinical course and a high number of potential comorbidities that may affect morbidity and mortality. Therefore, regular reevaluation of the patient is mandatory. This allows identification of characteristics aimed at maximizing the benefits for a specific patient or a subset of patients. Within this context, the role of the blood eosinophil count as a marker of inhaled corticosteroids response to prevent future exacerbations in patients who, despite appropriate bronchodilator therapy, still suffer from them has been proven to be a useful simple biomarker in medication selection. These advances support the concept of precision medicine, with the goal that patients get the right medicine at the right time for the right reason. Finally, recent studies have shown that early life events may be of critical relevance for the development of COPD. With this as a background, concepts to identify individuals at risk and early identification of cases have become an important objective of current research with the hope of maximizing the effects of therapy and the possibility of impacting disease progression., Competing Interests: Bartolome R Celli reports having received compensation from Advisory Boards and consultation fees from Glaxo Smith Kline, Boehringer-Ingelheim, Astra Zeneca, Novartis, Pulmonx, CHIESI, Menarini and Bayer. He does not have shares or interest in any company, neither does any member of his family. He has not received or had any relationship with tobacco money. Dave Singh has received personal fees from Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Epiendo, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, Pulmatrix, Sanofi, Teva, Theravance and Verona Claus Vogelmeier gave presentations at symposia and/or served on scientific advisory boards sponsored by AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GlaxoSmithKline, Grifols, Menarini, Novartis, Nuvaira, OmniaMed and MedUpdate, reports personal fees from Aerogen, grants, personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, CSl Behring, GlaxoSmithKline, Grifols, Novartis. Alvar Agusti: Research project funds: AZ, GSK, Menarini. Lectures: AZ, Chiesi, GSK, Menarini. AB: AZ, Chiesi, GSK, MSD, Menarini. The authors report no other conflicts of interest in this work., (© 2022 Celli et al.)

Chronic obstructive pulmonary disease (COPD) is a disease with an inflammatory phenotype with increasing prevalence in the elderly. Expanded population of mutant blood cells carrying somatic mutations is termed clonal hematopoiesis of indeterminate potential (CHIP). The association between CHIP and COPD and its relevant effects on DNA methylation in aging are mainly unknown. Analyzing the deep-targeted amplicon sequencing from 125 COPD patients, we found enhanced incidence of CHIP mutations (~20%) with a predominance of DNMT3A CHIP-mediated hypomethylation of Phospholipase D Family Member 5 ( PLD5 ), which in turn is positively correlated with increased levels of glycerol phosphocholine, pro-inflammatory cytokines, and deteriorating lung function.